1,4-Cyclohexadiene → HCID 178423003, compound

HRID 336848Notes

Reaction equation

HRID 336848 reaction equation
C([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:20]=[C:19]3[NH:21][N:22]=[C:23]([C:24]4[O:25][CH:26]=[CH:27][CH:28]=4)[C:18]3=[C:17]([C:29]3[CH:34]=[CH:33][C:32]([N:35]4[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH2:36]4)=[CH:31][CH:30]=3)[C:16]=2[C:48]#[N:49])=[CH:11][C:10]=1[CH3:50])C1C=CC=CC=1.C1CC=CCC=1>[Pd].CO.C(Cl)Cl>[C:48]([C:16]1[C:17]([C:29]2[CH:30]=[CH:31][C:32]([N:35]3[CH2:36][CH2:37][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:39][CH2:40]3)=[CH:33][CH:34]=2)=[C:18]2[C:23]([C:24]3[O:25][CH:26]=[CH:27][CH:28]=3)=[N:22][NH:21][C:19]2=[N:20][C:15]=1[C:12]1[CH:13]=[CH:14][C:9]([OH:8])=[C:10]([CH3:50])[CH:11]=1)#[N:49]

Participants

5

Reactant 2

HCID 123431,4-Cyclohexadiene3×HCID 178423004HCID 178423004, compound

Product 1

HCID 178423003HCID 178423003, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst3×HCID 21226129Dichloromethane methanolSolvent

Procedure

To a solution of 2.12 g (3.2 mmol) of tert-butyl 4-(4-(6-(4-(benzyloxy)-3-methylphenyl)-5-cyano-3-(furan-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-yl)phenyl)piperazine-1-carboxylate in a MeOH/CH2Cl2 mixture are added 0.41 g (0.38 mmol) of 10% Pd/C and 3 ml (2.57 g, 32.0 mmol) of 1,4-cyclohexadiene. The mixture is refluxed for 18 h, then 0.41 g (0.38 mmol) of 10% Pd/C and 3 ml (2.57 g, 32.0 mmol) of 1,4-cyclohexadiene are added, and the mixture is refluxed for an additional 24 h, 0.41 g (0.38 mmol) of 10% Pd/C and 3 ml (2.57 g, 32.0 mmol) of 1,4-cyclohexadiene are added and the mixture is again refluxed for 24 h. The mixture is then concentrated, dissolved in dichloromethane, filtered on Celite, then concentrated. The residue is purified by chromatography on silica (MeOH gradient in dichloromethane: 0 to 3%) to give 0.92 g (50%) of tert-butyl 4-(4-(5-cyano-3-(furan-2-yl)-6-(4-hydroxy-3-methylphenyl)-1H-pyrazolo[3,4-b]pyridine-4-yl)phenyl)piperazine-1-carboxylate in the form of yellow crystals.

Workup

  1. temperatureThe mixture is refluxed for 18 h
  2. temperaturethe mixture is refluxed for an additional 24 h
  3. temperaturethe mixture is again refluxed for 24 h
  4. concentrationThe mixture is then concentrated
  5. dissolutiondissolved in dichloromethane
  6. filtrationfiltered on Celite
  7. concentrationconcentrated
  8. customThe residue is purified by chromatography on silica (MeOH gradient in dichloromethane: 0 to 3%)

Sources & evidence

ORD record
ord-fb89e230378c4e62b54970760d3b9722
Source dataset
uspto-grants-2014_11
Patent number
US08889711B2

Reaction notes

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